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Membrane lipid composition directs the cellular selectivity of antimicrobial metallohelices
Despite very similar chemistries between the enantiomeric pairs (only difference is chirality), they often show distinct activities and cell selectivity profiles against Gram-positive and Gram-negative microbes. The effects of dose concentration and temperature on levels of intracellular accumulation in E. coli and S. aureus, studied via isotopic labelling, indicate that the metallohelices enter the microbial cells via passive diffusion, whereupon (as previously determined) they act on intracellular targets. Whilst the metallohelices with the shorter central hydrophobic regions accumulate less readily than those with the longer hydrophobic bridge in both E. coli and S. aureus cells when incubated at the same concentration, an order of magnitude less is required per cell to inhibit growth in E. coli, hence they are more active.
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